Safety and Tolerability Study of GSK1120212, a MEK Inhibitor, in Combination With Docetaxel, Erlotinib, Pemetrexed, Pemetrexed + Carboplatin, Pemetrexed + Cisplatin, or Nab-Paclitaxel

NCT01192165 | Completed Phase 1

• 2 other identifiers: 1134862012-000257-32
• Study Type: interventional
• Target: 169
• Locations: 4 countries
• Sites: 20

Brief Summary

The purpose of this study is to determine what dose of GSK1120212 can be given safely in combination with at least one other drug that is already approved to treat cancer. This study will test the safety of up to 6 different GSK1120212 study treatment combinations (GSK1120212 plus either docetaxel, erlotinib, pemetrexed, pemetrexed + carboplatin, pemetrexed + cisplatin, or nab-paclitaxel). The doses identified in this study may be used in future trials to test whether the combination treatment is a safe and effective therapy for subjects with metastatic lung and/or pancreatic cancers.

Conditions

Cancer

Keywords

Taxotere; Cisplatin; Carboplatin; Trametinib; GSK1120212; Tarceva; KRAS; Pemetrexed; MEK inhibitor; nab-Paclitaxel; Docetaxel; Alimta; Abraxane; Erlotinib

Outcome Measures

Primary Outcomes (1)

• To determine the safety, tolerability, and recommended phase II dosing regimen of each GSK1120212-based treatment combination

  Duration of study (approximately 3 years)

Secondary Outcomes (2)

• To characterize population pharmacokinetic parameters

  Duration of study (approximately 3 years)

• To evaluate the anti-tumor activity as assessed by tumor response rate according to RECIST v1.1

  Duration of study (approximately 3 years)

Study Arms (6)

Treatment Group 1

EXPERIMENTAL

Trametinib plus Docetaxel

Drug: Trametinib (GSK1120212); Drug: Docetaxel

Treatment Group 2

EXPERIMENTAL

Trametinib plus Erlotinib

Drug: Trametinib (GSK1120212); Drug: Erlotinib

Treatment Group 3

EXPERIMENTAL

Trametinib plus Pemetrexed

Drug: Trametinib (GSK1120212); Drug: Pemetrexed

Treatment Group 4

EXPERIMENTAL

Trametinib plus Pemetrexed and Carboplatin

Drug: Trametinib (GSK1120212); Drug: Pemetrexed; Drug: Carboplatin

Treatment Group 5

EXPERIMENTAL

Trametinib plus nab-Paclitaxel

Drug: Trametinib (GSK1120212); Drug: nab-Paclitaxel

Treatment Group 6

EXPERIMENTAL

Trametinib plus Pemetrexed and Cisplatin

Drug: Trametinib (GSK1120212); Drug: Pemetrexed; Drug: Cisplatin

Interventions

Trametinib (GSK1120212) DRUG

Investigational small molecule targeted therapy (MEK1/2 inhibitor)

Treatment Group 1; Treatment Group 2; Treatment Group 3; Treatment Group 4; Treatment Group 5; Treatment Group 6

Docetaxel DRUG

Chemotherapy

Treatment Group 1

Erlotinib DRUG

Small molecule targeted therapy (EGFR inhibitor)

Treatment Group 2

Pemetrexed DRUG

Chemotherapy

Treatment Group 3; Treatment Group 4; Treatment Group 6

Carboplatin DRUG

Chemotherapy

Treatment Group 4

nab-Paclitaxel DRUG

Chemotherapy

Treatment Group 5

Cisplatin DRUG

Chemotherapy

Treatment Group 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has a solid tumor. Expansion cohorts are limited to non-small cell lung cancer and/or pancreatic cancer with or without a KRAS mutation.
• Tumor progression following at least one prior standard therapy, the subject refuses standard therapy, or no standard therapy exists.
• The subject has a radiographically measurable tumor.
• The subject is able to carry out daily life activities without difficulty.
• The subject is able to swallow and retain oral medication.
• The subject does not have significant side effects from previous anti-cancer treatment.
• The subject has adequate organ and blood cell counts.
• Sexually active subjects must use medically acceptable methods of contraception during the course of the study.

You may not qualify if:

• The subject has had major surgery or received certain types of cancer therapy within 2-3 weeks before starting the study.
• The subject has a brain tumor.
• Current severe, uncontrolled systemic disease.
• History of clinically significant heart, lung, or eye/vision problems.
• The subject has high blood pressure that is not well-controlled with medication.
• The subject has a permanent pacemaker.
• The subject is pregnant or breastfeeding.
• Positive for Hepatitis B, Hepatitis C, or HIV.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (20)

GSK Investigational Site

Scottsdale, Arizona, 85259, United States

Location

GSK Investigational Site

Duarte, California, 91010, United States

Location

GSK Investigational Site

Sacramento, California, 95817, United States

Location

GSK Investigational Site

Denver, Colorado, 80218, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89169, United States

Location

GSK Investigational Site

Albany, New York, 12206, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29605, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Tyler, Texas, 75702, United States

Location

GSK Investigational Site

Norfolk, Virginia, 23502, United States

Location

GSK Investigational Site

Vancouver, Washington, 98684, United States

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Caen, 14033, France

Location

GSK Investigational Site

Marseille, 13385, France

Location

GSK Investigational Site

Saint-Herblain, 44805, France

Location

GSK Investigational Site

Toulouse, 31052, France

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Seoul, 135-710, South Korea

Location

Related Publications (1)

• Gandara DR, Leighl N, Delord JP, Barlesi F, Bennouna J, Zalcman G, Infante JR, Reckamp KL, Kelly K, Shepherd FA, Mazieres J, Janku F, Gardner OS, Mookerjee B, Wu Y, Cox DS, Schramek D, Peddareddigari V, Liu Y, D'Amelio AM Jr, Blumenschein G Jr. A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2017 Mar;12(3):556-566. doi: 10.1016/j.jtho.2016.11.2218. Epub 2016 Nov 19.

  PMID: 27876675 DERIVED

Related Links

• Results for study 113486 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Neoplasms

Interventions

trametinib; Docetaxel; Erlotinib Hydrochloride; Pemetrexed; Carboplatin; 130-nm albumin-bound paclitaxel; Cisplatin

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2010
• First Posted: August 31, 2010
• Study Start: September 14, 2010
• Primary Completion: October 7, 2013
• Study Completion: October 7, 2013
• Last Updated: November 13, 2017

Record last verified: 2017-11

Locations

US (13); KR (2); CA (1); FR (4)